'Outcomes of genetic testing in the London MND Center: the importance of achieving timely results and correlations to family history'.

Background: Despite recognition of the importance of genetic factors in the pathogenesis of MND and the increasing availability of genetic testing, testing practice remains highly variable. With the arrival of gene-targeted therapies there is a growing need to promptly identify actionable genetic results and patient death before receipt of results raises ethical dilemmas and limits access to novel therapies. Objective: To identify pathogenic mutations within a London tertiary MND center and their correlation with family history. To record waiting times for genetic results and deaths prior to receipt of results. Methods: In this series of 100 cases, genetic testing was offered to all patients with an MND diagnosis from the tertiary clinic. Data on demographics, disease progression and a detailed family history were taken. Time to receipt of genetic results and patient deaths prior to this were recorded.  Results: Of the 97 patients who accepted testing a genetic cause was identified in 10%, including seven C9orf72 and two positive SOD1 cases. Only three patients with positive genetic findings had a family history of MND, although alternative neurological diagnoses and symptoms in the family were frequently reported. 14% of patients who underwent testing were deceased by the time results were received, including one actionable SOD1 case.  Conclusions: Genetic testing should be made available to all patients who receive an MND diagnosis as family history alone is inadequate to identify potential familial cases. Time to receipt of results remains a significant issue due to the limited life expectancy following diagnosis.

A retrospective data analysis on the induction medications used in trauma rapid sequence intubations and their effects on outcomes.

PURPOSE: Rapid sequence intubation (RSI) in trauma patients is common; however, the induction agents used have been debated. We determined which induction medications were used most frequently for adult trauma RSIs and their associations with hemodynamics and outcomes. We hypothesized that etomidate is the most commonly used induction agent and has similar outcomes to other induction agents. METHODS: This retrospective review at two U.S. level I trauma centers evaluated adult trauma patients undergoing RSI within 24 h of admission, between 01/01/2016 and 12/31/2017. We compared patient characteristics and outcomes by induction agent. Comparisons on the primary outcome of in-hospital mortality and secondary outcomes of peri-intubation hypotension, hospital and ICU length of stay (LOS), ventilator days, and complications used logistic regression or negative binomial regression. Regression models adjusted for hospital site, age, patient severity measures, and intubation location. RESULTS: Among 1303 trauma patients undergoing RSI within 24 h of admission, 948 (73%) were intubated in the emergency department (ED) and 325 (25%) in the operating room (OR). The most common induction agents were etomidate (68%), propofol (17%), and ketamine (11%). In-hospital mortality was highest in the etomidate group (25.5%), followed by ketamine (17%), and propofol (1.8%). CONCLUSION: Etomidate was most commonly used in ED intubations; propofol was most used in the OR. Compared to propofol, patients induced with etomidate had higher mortality and complication rates. Findings should be interpreted with caution given limited generalizability and residual confounding by indication.

Penetrating Cardiac Injury from Crossbow Successfully Treated With Cardiac Autotransplantation.

A middle-aged male patient presented with self-inflicted penetrating cardiac injury from 2 crossbow bolts causing injury to multiple cardiac structures and surrounding great vessels. He was successfully treated with peripheral cannulation for cardiopulmonary bypass, median sternotomy, hypothermic circulatory arrest, autotransplantation of the heart, and repair of all intracardiac injuries.

The use of computed tomography imaging for abdominal seatbelt sign: A single-center, prospective evaluation.

INTRODUCTION: Guidelines surrounding abdominal seat belt sign (SBS) were made prior to the use of modern computed tomography (CT) imaging. We sought to prospectively determine whether a negative CT scan is associated with the absence of hollow viscus injury (HVI), and we hypothesized that trauma patients with an abdominal SBS without CT imaging findings would not have a hollow viscus injury (HVI). METHODS: A prospective cohort of patients with SBS was compiled over one year. Subjects were divided into those with and without HVI. Covariate distributions were summarized by group. Bivariate tests and logistic regression were used to investigate associations between covariates and HVI. RESULTS: Of 220 patients with SBS, the incidence of HVI was 7% (n = 15). Radiographic findings were strongly associated with HVI and no patients with a negative CT scan had HVI. Free fluid was seen in 80% (12) of patients with HVI, whereas it was found in only 11% (23) without injury. A composite variable for negative CT scan was found to be associated with the absence of HVI: (Fisher's exact 1-tailed p, doubled = 0.014). CONCLUSION: In this study, the incidence of HVI with SBS is lower than previously reported, and no patients with negative CT imaging required an operation for HVI-suggesting there is a population of patients with SBS who could be discharged from the emergency room. A prospective multicenter study is needed to confirm these findings.

The role of the American Society of anesthesiologists physical status classification in predicting trauma mortality and outcomes.

BACKGROUND: Trauma prediction scores such as Revised Trauma Score (RTS) and Trauma and Injury Severity Score (TRISS)) are used to predict mortality, but do not include comorbidities. We analyzed the American Society of Anesthesiologists physical status (ASA PS) for predicting mortality in trauma patients undergoing surgery. METHODS: This multicenter, retrospective study compared the mortality predictive ability of ASA PS, RTS, Injury Severity Score (ISS), and TRISS using a complete case analysis with mixed effects logistic regression. Associations with mortality and AROC were calculated for each measure alone and tested for differences using chi-square. RESULTS: Of 3,042 patients, 230 (8%) died. The AROC for mortality for TRISS was 0.938 (95%CI 0.921, 0.954), RTS 0.845 (95%CI 0.815, 0.875), and ASA PS 0.886 (95%CI 0.864, 0.908). ASA PS + TRISS did not improve mortality predictive ability (p = 0.18). CONCLUSIONS: ASA PS was a good predictor of mortality in trauma patients, although combined with TRISS it did not improve predictive ability.

Thyroid Trauma-A National Analysis of Incidence, Mortality, and Concomitant Injury.

BACKGROUND: Traumatic injury to the thyroid is rare with no large national studies in the literature. We sought to describe the incidence of traumatic thyroid injury and to compare injury characteristics, operative interventions, and outcomes of isolated thyroid versus thyroid and concomitant neck injury. METHODS: The National Trauma Data Bank (2007-2015) was used to identify patients with thyroid injury. Concomitant injury to surrounding neck structures included the trachea, esophagus, carotid arteries, cervical spine vertebrae, or vertebral arteries. A multivariable logistic regression analysis was performed. RESULTS: The incidence of thyroid injury was <0.1%. Of these, 59.7% of patients had isolated thyroid injury and 40.3% had thyroid and concomitant neck injury. Most patients in both groups had a penetrating mechanism (75.8% and 85.6%). Thyroid operative intervention was rare in both groups (isolated thyroid injury 19.3%, thyroid and concomitant neck injury 22.1%). Direct thyroid repair was the most common type of surgical intervention performed (isolated thyroid 13.1% versus thyroid and concomitant neck injury 15.1%; P = 0.280), whereas total thyroidectomy was only performed in a single patient. Mortality was decreased for patients with isolated thyroid injury compared with thyroid and concomitant neck injury (8.9% versus 19%; P < 0.001). CONCLUSIONS: Thyroid injury in trauma patients is extremely rare and occurs more frequently with penetrating trauma. Isolated thyroid trauma is associated with a lower risk of mortality, compared to thyroid trauma with concomitant neck injury. Most thyroid injury is treated nonoperatively, and when operative intervention is required, direct thyroid repair is most commonly performed.

Early Versus Late Pulmonary Embolism in Trauma Patients: Not All Pulmonary Embolisms are Created Similarly.

BACKGROUND: Pulmonary embolism (PE) is an uncommon complication occurring in up to 5% of trauma patients. In small previous studies, patients with long-bone fractures were associated with a higher risk of early PE while those with severe head injuries were at higher risk for late PE. MATERIALS AND METHODS: This was a retrospective analysis at a single level I trauma center from 2010 to 2017. Patients with early PE (≤4 d) were compared to those with late PE (>4 d) using bivariate analysis and multivariable logistic regression analysis. We sought to confirm risk factors for early and late PE, hypothesizing that early PE is associated with long-bone fractures and late PE is associated with above-the-knee deep venous thrombosis (DVT). RESULTS: From 12,833 trauma admissions, 76 patients (0.6%) had a PE. Of these, 33 (43.4%) had an early PE and 43 (54.6%) were diagnosed with late PE. After adjusting for covariates, independent risk factors for late PE included above-the-knee DVT (odds ratio [OR] = 12.01, confidence interval [CI] = 1.34-107.52, P = 0.03), blood transfusion (OR = 8.99, CI = 1.75-46.22, P = 0.009), and craniotomy (OR = 8.82, CI = 1.03-75.97, P = 0.04), while the only independent risk factor for early PE was smoking (OR = 4.56, CI 1.06-19.66, P = 0.04). Severe head injury and long-bone fractures were not risk factors for early or late PE (P > 0.05) CONCLUSIONS: The strongest risk factor for late PE is above-the-knee DVT. Contrary to previous reports, long-bone extremity fractures and severe head injuries are not associated with early or late PE. The only risk factor for early PE was a history of smoking.

National Trends of Thoracic Endovascular Aortic Repair versus Open Thoracic Aortic Repair in Pediatric Blunt Thoracic Aortic Injury.

BACKGROUND: Blunt thoracic aortic injury (BTAI) occurs in <1% of all trauma admissions. Thoracic endovascular aortic repair (TEVAR) has become the preferred treatment modality in adult patients with BTAI, but its use in pediatrics is currently not supported by device manufacturers and lacks United States Food and Drug Administration approval. We hypothesized that there would also be an increased use of TEVAR in the pediatric population, thus conferring a lower risk of mortality compared with open thoracic aortic repair (OTAR). METHODS: The National Trauma Data Bank (2007-2015) was queried for patients ≤17 years with BTAI. The primary outcomes were the incidences of TEVAR and OTAR. Secondary outcome was risk of mortality in those undergoing intervention. A multivariable logistic regression model was used to determine the risk of mortality in OTAR versus TEVAR. RESULTS: We identified 650 pediatric BTAI patients with 159 (24.5%) undergoing intervention. Of these, 124 underwent TEVAR (78.0%) and 35 (22.0%) underwent OTAR. The rate of TEVAR steadily increased from 2007 to 2015 (15.4% vs. 27.1%, P < 0.001). Patients receiving OTAR and TEVAR had a similar injury severity score and rate of hypotension on admission (P > 0.05). Compared with OTAR, TEVAR patients had a higher rate of any traumatic brain injury (TBI) (63.7% vs. 37.1%, P = 0.005) and shorter hospital and intensive care unit length of stay (LOS) (16.4 vs. 21.4 days, P = 0.02; 10.1 vs. 12.2 days, P = 0.01). TEVAR and OTAR, even when stratified by ≤14 years and 15-17 years, had no difference in risk for mortality (odds ratio 1.20, confidence interval 0.29-5.01, P = 0.80). CONCLUSIONS: The rate of TEVAR in pediatric BTAI nearly doubled from 2007 to 2015. Compared with OTAR, TEVAR was associated with a shorter hospital LOS despite a higher rate of TBI. There was no difference in risk for mortality between TEVAR and OTAR. Longitudinal studies to determine the long-term efficacy and complication rates, including reintervention, development of endoleak, and/or need for further operations, are needed as this technology is being rapidly adopted for pediatric trauma patients.

National risk factors for blunt cardiac injury: Hemopneumothorax is the strongest predictor.

BACKGROUND: Blunt cardiac injury (BCI) can occur after chest trauma and may be associated with sternal fracture (SF). We hypothesized that injuries demonstrating a higher transmission of force to the thorax, such as thoracic aortic injury (TAI), would have a higher association with BCI. METHODS: We queried the National Trauma Data Bank (NTDB) from 2007-2015 to identify adult blunt trauma patients. RESULTS: BCI occurred in 15,976 patients (0.3%). SF had a higher association with BCI (OR = 5.52, CI = 5.32-5.73, p < 0.001) compared to TAI (OR = 4.82, CI = 4.50-5.17, p < 0.001). However, the strongest independent predictor was hemopneumothorax (OR = 9.53, CI = 7.80-11.65, p < 0.001) followed by SF and esophageal injury (OR = 5.47, CI = 4.05-7.40, p < 0.001). CONCLUSION: SF after blunt trauma is more strongly associated with BCI compared to TAI. However, hemopneumothorax is the strongest predictor of BCI. We propose all patients presenting after blunt chest trauma with high-risk features including hemopneumothorax, sternal fracture, esophagus injury, and TAI be screened for BCI. SUMMARY: Using the National Trauma Data Bank, sternal fracture is more strongly associated with blunt cardiac injury than blunt thoracic aortic injury. However, hemopneumothorax was the strongest predictor.

National Trends of Thoracic Endovascular Aortic Repair Versus Open Repair in Blunt Thoracic Aortic Injury.

BACKGROUND: Blunt thoracic aortic injury (BTAI) occurs in <1% of all trauma admissions. Considering the advent of multiple thoracic endovascular aortic repair (TEVAR) devices over the past decade, improved outcomes of TEVAR supported in the literature, rapid diagnosis, and improved preoperative planning of BTAI using computed tomography imaging, we hypothesized that the national incidence of TEVAR in BTAI has increased while open repair has decreased. In addition, we hypothesized that the mortality risk in BTAI patients undergoing TEVAR would be lower than open repair. METHODS: This was a retrospective analysis of the National Trauma Data Bank from 2007 to 2015. The primary end points of interest included the incidence of TEVAR and open repair, as well as mortality in BTAI patients undergoing intervention. Covariates were included in a multivariable analysis to determine risk for mortality in BTAI patients undergoing open repair versus TEVAR. RESULTS: We identified 3,628 BTAI patients undergoing intervention. Of these, 3,226 underwent TEVAR (87.9%), and 445 (12.1%) underwent open repair. Compared with open repair, TEVAR had a shorter mean length of stay (LOS) (19.8 vs. 21.3 days, P < 0.05) and lower rates of acute kidney injury (AKI) (5.6% vs. 9.0%, P < 0.05) and mortality (8.8% vs. 12.8%, P < 0.05). Open repair had greater risk for mortality than TEVAR (odds ratio = 1.63, confidence intervals = 1.19-2.23, P < 0.05). CONCLUSIONS: The rate of open repair decreased from 7.4% in 2007 to 1.9% in 2015, whereas TEVAR increased from 12.1 to 25.7% during the same time period. We confirmed previous findings that endovascular repair is associated with decreased mortality, LOS, and major complications, including AKI. Future investigations should focus on identifying the ideal patient candidate for TEVAR and elucidate precise indications for TEVAR in BTAI.

Unusual cardiac paraganglioma mimicking an atypical carcinoid tumor of the lung.

We present a case of unusual cardiac paraganglioma (PG) initially misdiagnosed as atypical carcinoid tumor of the lung and discuss key clinical and pathologic characteristics that guide surgical management of these rare chromaffin cell tumors. A 64-year-old female with persistent cough and back pain was found to have a 4 cm × 3 cm mass abutting multiple cardiopulmonary structures. A biopsy was performed at an outside institution and pathology reported "atypical neuroendocrine carcinoma, consistent with carcinoid". The patient was transferred to our institution and pericardial resection with right pneumonectomy was performed to excise the tumor. Histology of the mass was that of PG with multiple ethanol embolizations. Immunohistochemical examination revealed that type I (chief) cells were positive for neuroendocrine markers (chromogranin A and synaptophysin), while type II (sustentacular) cells were positive for S100. There was no evidence of atypical carcinoid tumor in the lung. PG is an entity of chromaffin cell tumors that often affects the adrenal glands and carotid body. PG rarely occurs in the thoracic region, accounting for just 1-2% of all PG. Proper diagnosis of cardiac PG is challenging owing to its rare prevalence, subtle symptoms of presentation, and the neuroendocrine histopathological features it shares with atypical carcinoids. These tumors are typically benign and are best treated by surgical resection. Our report examines the approach to appropriate diagnosis of cardiac PG vs. atypical carcinoid, preoperative management, and surgical treatment by describing successful resection through thoracotomy without the use of cardiopulmonary bypass.

911 Emergency Medical Services and Re-Triage to Level I Trauma Centers.

BACKGROUND: Interfacility transfer of undertriaged patients to higher-level trauma centers has been found to result in a delay of appropriate care and an increase in mortality. To address this, for the last 10 years our region has used 911 emergency medical services (EMS) paramedics for rapid re-triage of undertriaged patients to our institution's Level I trauma center. We sought to determine whether using 911 EMS for re-triage to our institution was associated with worse outcomes-with mortality as the primary end point-compared with direct EMS transport from point of injury. STUDY DESIGN: We retrospectively reviewed all trauma activations to our institution during a 16-month period; 3,394 active traumas were analyzed. RESULTS: Two hundred and seventy patients (8%) arrived via 911 EMS re-triage and 3,124 (92%) arrived via direct EMS transport. Total EMS transport time was significantly longer (122.5 minutes vs 33.7 minutes; p < 0.001) between the 2 groups, but there was no significant difference in mortality rates (4.1% vs 3.6%; p = 0.67). CONCLUSIONS: These data show that although using 911 EMS for re-triage is associated with an increase in total transport time, it does not result in an increase in mortality compared with direct EMS transport. We conclude that the use of 911 EMS can be considered a safe method to re-triage patients to higher-level trauma centers.

In vivo structure-function studies of human hepatic lipase: the catalytic function rescues the lean phenotype of HL-deficient (hl-/-) mice.

The lean body weight phenotype of hepatic lipase (HL)-deficient mice (hl(-/-)) suggests that HL is required for normal weight gain, but the underlying mechanisms are unknown. HL plays a unique role in lipoprotein metabolism performing bridging as well as catalytic functions, either of which could participate in energy homeostasis. To determine if both the catalytic and bridging functions or the catalytic function alone are required for the effect of HL on body weight, we studied (hl(-/-)) mice that transgenically express physiologic levels of human (h)HL (with catalytic and bridging functions) or a catalytically-inactive (ci)HL variant (with bridging function only) in which the catalytic Serine 145 was mutated to Alanine. As expected, HL activity in postheparin plasma was restored to physiologic levels only in hHL-transgenic mice (hl(-/-)hHL). During high-fat diet feeding, hHL-transgenic mice exhibited increased body weight gain and body adiposity relative to hl(-/-)ciHL mice. A similar, albeit less robust effect was observed in female hHL-transgenic relative to hl(-/-)ciHL mice. To delineate the basis for this effect, we determined cumulative food intake and measured energy expenditure using calorimetry. Interestingly, in both genders, food intake was 5-10% higher in hl(-/-)hHL mice relative to hl(-/-)ciHL controls. Similarly, energy expenditure was ~10% lower in HL-transgenic mice after adjusting for differences in total body weight. Our results demonstrate that (1) the catalytic function of HL is required to rescue the lean body weight phenotype of hl(-/-) mice; (2) this effect involves complementary changes in both sides of the energy balance equation; and (3) the bridging function alone is insufficient to rescue the lean phenotype of hl(-/-)ciHL mice.